Citalopram is a kind of important antidepressant, and is a selective serotonin (5-HT) reuptake inhibitor. It has advantages such as rapid onset, obvious antidepressant effect, and little side effects, etc. Its isomer having single optical activity, escitalopram (S-citalopram), has anti-proliferative effect 100 times of that of its isomer with an opposite configuration, R-citalopram. Therefore, escitalopram (S-citalopram) has better efficacy and smaller dosage. Currently, S-citalopram gradually occupies larger market share of antidepressants. The structures of citalopram (I) and its isomer having single optical activity, i.e. S-citalopram (II), are as follows:

A main route for preparing citalopram is cyclizing citalopram diol (IV) to obtain citalopram (I).
A main route for preparing S-citalopram is obtaining S-citalopram diol (V) through chiral resolution of citalopram diol (IV), and then cycling S-citalopram diol (V) to obtain S-citalopram (II).
The structural formulae of citalopram diol (IV) and S-citalopram diol (V) are as follows:

It follows that citalopram diol (IV) is a key intermediate for the industrial production of citalopram and S-citalopram.
U.S. Pat. No. 4,650,884 reports that citalopram diol (IV) is obtained by using 5-cyanophthalide as the starting material, which is subjected to two Grignard addition reactions with p-fluorophenyl magnesium halide and N,N-dimethylaminopropyl magnesium halide. The synthetic route is as follows:

The method reported in the above patent mainly suffers from low conversion rate, substantial side reactions, low yield, and low purity of the product. The possible reasons are as follows: (1) there are many reaction sites for the Grignard addition reactions, and the selectivity of the reactions is poor; (2) the intermediate obtained after the first addition with p-fluorophenyl magnesium halide is a ketone, resulting in a large steric hindrance during the following addition with N,N-dimethylaminopropyl magnesium halide, and thus the conversion rate is low; and (3) competitive reactions exist between the two Grignard reagents, which result in many by-products.